It’s a story right out of one of the X-Men movies—people who are born with genetic differences that give them an evolutionary advantage over their fellows. In this case, that advantage is over catastrophic disease.
We’re all familiar with how most disease research is accomplished: scientists study those who are afflicted with a particular disease to see how it affects them overall and how it affects their individual biological systems. But Dr. Stephen Friend of Sage Bionetworks in Seattle led a team of scientists from New York’s Icahn School of Medicine at Mount Sinai on a different tack—to study individuals who should suffer from or should have died from disease, but never became sick in the first place. To do this, they examined the genetic profiles of nearly 600,000 subjects from 12 previous genetic studies and looked closely at 584 Mendelian diseases (diseases caused by single gene mutations that are inherited according to Gregor Mendel’s Laws).
Mendelian genetics is the type of genetics most high school students studied in biology class. Remember Punnett squares? That’s Mendelian genetics—gene traits that are dictated by the alleles of a single gene. Let’s review and look at a very simplified version of eye colour. If a parent has brown eyes, they are expressing the dominant allele of the eye colour gene, which is brown (B). But everyone has two copies of that gene, one donated from their mother and one from their father. Because of the dominant brown allele (B), the second allele could be a second dominant brown allele (B) or a recessive blue allele (b) masked by the dominant brown. In high school biology terms, this parent could be BB, or Bb; both allele pairs would result in brown eyes. Only a parent with blue eyes is guaranteed to be bb, because two recessive genes will allow the recessive colour to show instead of being masked by the dominant colour. But if you pair two brown eyed parents, both of whom come from a brown eyed and blue eyed parent themselves, you will have two parents who are Bb and the below Punnett square shows what their offspring statistically should look like.
This is my husband and I exactly. Both ours mother have brown eyes, both fathers have or had blue eyes, but we both have brown eyes, therefore, we must both be Bb. We have two daughters, one with green eyes (genetically blue in this simple example; the green colour comes from additional masking gene alleles) and one with brown eyes.
Mendelian diseases are similarly governed by a single mutation on a single gene. Some of the diseases they looked at were Cystic Fibrosis (a disorder of the exocrine glands that affects the lungs, pancreas, intestine, liver, and kidneys), Smith-Lemli-Opitz syndrome (a mutation in the cholesterol pathway which leads to significant developmental delays or even death), epidermolysis bullosa (a devastating blistering skin condition), familial dysautonomia (a disorder of the nervous system), and Pfeiffer syndrome (which causes the bones in the skull to fuse early, leading to a misshapen head, bulging eyes and abnormal brain development). And what researchers found both surprised and delighted them. Of the 589,306 subjects tested, looking at 874 genes that guarantee the development of disease, they found 13 individuals who genetically had one of the mutations and yet had no indications of disease. For all intents and purposes, they are resistant.
Yes, I hear you cry: 13 people out of 589,306? That’s only 0.0022%, so what’s the big deal? The big deal is the answers these people may hold. Why aren’t they sick? What is it about their genetic makeup that counteracts a devastating mutation that might have already killed them otherwise? Discovering those secrets could potentially help the 70,000 people worldwide living with Cystic Fibrosis, desperately waiting for lung transplants while fighting trying to take their next breath. It could help the more than 500,000 people worldwide who suffer from epidermolysis bullosa, whose skin blisters and peels off at the lightest touch, and who can die from cancer or from infection of the exposed derma.
It's clear that 13 subjects are not enough to power any kind of real scientific study, but they are a promising start. Scientists now hope to recruit healthy volunteers that are willing to share their genetic information. Interested? Then the Reliance Project may be for you. Stop by the site, and take a look and join me in signing up. As they say at the Reliance Project: ‘Join the search. Be a hero.’ You might just save a life along the way.
Photo credit – Wikimedia Commons